Increased physical activity accompanies carbohydrate preference in a B6.CAST-17 sub-congenic mouse strain. Mus musculus

A C57BL6/J (B6) x CAST/Ei (CAST) strain intercross was used to identify the first mammalian QTL for macronutrient-specific intake (carbohydrate and fat) and for total energy intake. A region on proximal Chromosome 17 revealed two significant QTL that co-localized for increased macronutrient intake-carbohydrate (Mnic1) and total kilocalorie intake (Kcal2), adjusted for body weight. An interval-specific congenic strain, B6.CAST-17, was then developed which verified the QTL. A new sub-congenic strain was developed which retained the linked traits. Important new findings emerged shows that this congenic interval confers an activity phenotype, i.e., mice carrying the differential segment have 20% higher spontaneous physical activity levels compared with the host B6 strain. We hypothesize that this Chromosome 17 QTL is either encoded by a single gene locus that determines both food intake and physical activity, or by two or more genes, each determining a sub-phenotype of energy balance. Microarray analysis of skeletal muscle and hypothalamus in congenic and wild type B6 mice was carried out to identify potential candidate genes for the activity and food intake behavior. Keywords: macronutrient-specific intake, sub-congenic strain Overall design: Hypothalamus and skeletal muscle RNA were obtained from three male B6.CAST-17 homozygous congenic mice and three male wild type B6 mice. Each strain was represented by three mice, thus three biological replicates were analyzed for each strain.